1-Hydroxy-4-aminoadamantane is a compound useful as a raw material for, or an intermediate for synthesizing a medicament and, for example, can be utilized as an intermediate for synthesizing a compound having 11 β-hydroxy steroid dehydrogenase inhibiting activity described in Patent Document 1, Patent Document 2 and Patent Document 3.
Non-Patent Document 1 and Non-Patent Document 2 disclose a process for producing 1-hydroxy-4-aminoadamantane by reacting 2-aminoadamantane with a mixture of nitric acid and sulfuric acid to perform hydroxylation. In the reaction, a ratio of produced diastereomers is advantageous for a syn isomer, and syn isomer:anti isomer is 3:1 to 1:1.
Table 1, Entry 6 in Non-Patent Document 3 discloses that 5-hydroxy-2-adamantanone and benzylamine are reacted in the presence of H2/5% Pt—C, and anti isomer:syn isomer is obtained at 1:1. In addition, Table 2, Entry 8 discloses that 5-hydroxy-2-adamantanone and benzylamine are reacted in the presence of H2/5% Rh—C and Al (iOPr)3, and anti isomer:syn isomer is obtained at 2.7:1. A production ratio of anti isomer/syn isomer in these two experimental examples was measured by 1H-NMR, and any compounds were not isolated.
Patent Document 1 discloses a process for producing an anti isomer of 1-hydroxy-4-aminoadamantane by reacting 5-hydroxy-2-adamantanone and L (−)-1-phenyl-ethylamine in the presence of a heterogeneous catalyst (e.g. rhodium supported on carbon), purifying the resulting diastereomers by column chromatography, isolating an anti isomer, and subjecting the isomer to debenzylation.
Patent Document 2 discloses a process for producing an anti isomer by reacting 5-hydroxy-2-adamantanone and ammonia/methanol in the presence of sodium borohydride, amidating the resulting diastereomer mixture, and purifying the resulting amido isomer by column chromatography.
Patent Document 3 discloses a process for producing an anti isomer by subjecting a diastereomer mixture of 1-hydroxy-4-aminoadamantane, and carboxylic acid to amidation, and purifying the resulting amido isomer by column chromatography.
In the processes described in any document, it is necessary to purify the resulting diastereomer mixture by column chromatography, and industrial utilization was difficult.    [Non-Patent Document 1] Zhurnal Organicheskoi Khimii 1976, 12(11), 2369    [Non-Patent Document 2] Khimiko Farmatsevticheskii Zhurnal 1986, 20(7), 810    [Non-Patent Document 3] Tetrahedron Letters 47 (2006) 8063    [Patent Document 1] WO 04/056745    [Patent Document 2] WO 05/108368    [Patent Document 3] WO 05/016877